Characterizing microbial communities in the human gut and soil to understand their roles in health, disease and the environment

Filed Under: MolE PhDNews

Alex Carr
MolE PhD Student Alex Carr

Alex Carr is a 3rd year molecular engineering Ph.D. student co-advised by UW affiliated investigators Drs. Sean Gibbons and Nitin Baliga at the Institute for Systems Biology. We recently spoke with Carr about his research and his experience in the Molecular Engineering (MolE) Ph.D. program.

How did you come to pursue a Ph.D. in molecular engineering?

I got my undergraduate degree in chemistry from UC San Diego where I worked in an x-ray crystallography lab characterizing bacterial enzymes. During that time, I also worked as an intern in a bio-analytical chemistry lab at the pharmaceutical company Takeda. After graduating, I wanted to gain some more biologically relevant research experience so I became a research associate at UC Berkeley in the lab of Adam Arkin. There I worked on a project involving characterization and modeling of interspecies interactions among a set of twelve human gut microbes. At that point, I realized that to really advance in science and continue doing this kind of research, I would need to go to graduate school.

Given my background in chemistry and my research experience in biology, I wanted to find a graduate program that interfaced with both disciplines. The inherent interdisciplinarity of molecular engineering and the broad range of faculty I could potentially work with in the MolE program were definite pluses, as was the opportunity to live in a city like Seattle.

What led you to conduct your doctoral research at the Institute for Systems Biology (ISB)?

When I arrived at the UW, I was pretty set on doing synthetic biology research, but at the end of my first year I found myself having done all my rotations, without having found a lab that was the right fit. Paul Neubert, our graduate program coordinator, encouraged me to explore opportunities outside of UW at institutions such as the Fred Hutch Research Institute and ISB, both of which are located in the South Lake Union area of downtown Seattle.

It ended up being quite serendipitous. As a member of the labs of ISB investigators Dr. Sean Gibbons and Dr. Nitin Baliga, I am able to build on my previous research experience by studying microbial ecology through a systems biology lens using both computational and experimental methodologies. While both labs study microbial communities, the Gibbon's lab focuses on the human gut microbiome while the Baliga lab is interested in microbial communities in soil.

What is it like to be a graduate student at ISB?

ISB is mostly postdocs and staff scientists, though the grad student population has been slowly growing over the past few years. Until recently, I was the only graduate student in both the Gibbons and Baliga labs. ISB puts a strong emphasis on collaborative research, so there are many opportunities to work with scientists in other labs. As a result, I find it easy to reach out to others and get help when I need it. It has been a great environment to learn in.

Tell us about your research.

My research focuses on developing a deeper understanding of the complex interspecies dynamics of soil and human gut microbial communities through the characterization of individual species, synthetic consortia, and the application of novel computational approaches. I am primarily interested in how interspecies interactions and environmental factors modulate the functions of microbial communities, the ways by which communities adapt to changes in their environment, and the roles these communities play in the soil and human gut ecosystems.

In the Gibbons lab, I am leveraging publicly available data and a novel metabolic modeling framework to develop a deeper understanding of how the composition of the human gut microbiome can promote or prevent infection by the pathogen Clostridioides difficile (C. diff). C. diff infections are a major issue in clinical settings and are generally associated with loss of diversity in gut microbiome (typically as a result of antibiotic use). By modeling community level metabolic interactions, I hope to gain insights into the competitive and cooperative interactions that make certain microbes (and their metabolites) critical players in fighting off C. diff infections.

In the Baliga lab, I am investigating the roles nitrate reducing-bacteria play in the soil environment. My research is part of a larger project within ENIGMA, a consortium funded by the Department of Energy, to understand how nitrate contamination at a Superfund site near the Oak Ridge National Lab in Tennessee impacts the ecology of the soil. Generally, microbes in the soil convert nitrate and turn it into nitrogen gas; however, these microbe communities are unable to survive the harsh conditions present at the superfund site. As a result, instead of producing nitrogen gas, they produce the greenhouse gas nitrous oxide. A better understanding of how these microbial communities adapt to changes in their environment and the roles they play, as well as how interspecies interactions and environmental factors facilitate the formation and functions of microbial communities, will help scientists develop potential solutions for cleaning up contaminated sites.

How has your research been affected by COVID?

For the first few months of quarantine, like everyone else, I mostly worked from home. I used the opportunity to work on a manuscript I had been putting off. My project in the Gibbons lab is entirely computational so I could pretty easily continue that work from home, but my research in the Baliga lab had to be halted for several weeks because it involves culturing microbes. Luckily, at this point I am able go into lab with the appropriate safety precautions.

What have you enjoyed most about your graduate school experience?

One of my favorite things, which I think is quite specific to this program, is the flexibility. I can take almost any class and work with almost any investigator at the UW which has allowed me to tailor my training and experiences to my interests. More generally, I appreciate that as a graduate student I am able to tackle interesting problems and discover things that were previously unknown.

You're only in your third year, but do you know what you want to do after finishing graduate school?

I know that I want to continue doing research, most likely in industry, either at a biotech startup or larger pharmaceutical company. Through my own research, and the coursework I've taken as part of the MolE data science option, I've learned a lot about computational methodology and am very interested in pursuing a career as a computational biologist.

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